Collagen synthesis and degradation must be carefully regulated in order to permit the development of a normally functioning organism and for successful homeostatic mechanisms. Indeed, morphogenetic and repair processes cannot tolerate even small deviations from an appropriate balance in these opposing processes without undesirable consequences. Collagen biogenesis and the dynamics of metabolism appropriate to a given tissue can be understood best by a precise biochemical definition of the steps involved and by localization of these steps to subcellular structures. It is therefore our aim to examine, in as detailed a manner as possible (a) the biosynthesis and structure of procollagen; (b) the transcellular secretory pathway for this protein and the metabolic requirements for secretion; (c) the conversion of procollagen to collagen by limited proteolytic steps; (d) the manner in which these processes may be regulated by the extracellular environment: and (e) the role of disorders of biosynthesis in human disease. Insofar as possible these studies will be performed in cell and organ cultures, systems which offer greater simplicity and flexibility for experimentation than the whole organism. An important purpose of this research is to identify points in the biosynthetic pathway at which physiological controls are exerted. It is expected that such information will be useful in the elucidation of disorders of connective tissue function in man and in the design of rational therapy of such disorders. BIBLIOGRAPHIC REFERENCES: Kruse, N. J., and Bornstein, P. The metabolic requirements for transcellular movement and secretion of collagen. J. Biol. Chem. 250: 4841-4847 (1975). Murphy, W. H., von der Mark, K., McEneany, L. S. G., and Bornstein, P. Characterization of procollagen-derived peptides unique to the precursor molecule. Biochemistry 14: 3243-3250 (1975).